Host defense amphipathic peptides found in eukaryotic cells have diverse activity in humans and other species originating from their antibiotic, anticancer and anti-inflammatory activity. These peptides oligomerize with the phospholipid cell membrane and cell organelles that result in pore formation and subsequently cause cell death. Such peptides have been explored extensively for cancer therapy owing to their wide-spectrum lytic properties and because cancer cells are not likely to develop resistance to such materials. Unfortunately, in vivo application of these materials has been compromised by serious off-target toxicity.
Melittin, derived from the toxin of the honey bee, Apis mellifera, is one of the most promising amphipathic water-soluble α-helical cationic polypeptides. Melittin attacks the lipid membranes resulting in physical and chemical disruption of membrane structure leading to profound compromise of the cell permeability barrier by lysis. It is a very attractive cancer therapeutic agent because cancer cells are less likely to develop resistance to these peptides. Unfortunately, however, it is a nonspecific cytolytic peptide, and, as with other such peptides, this leads to off target-effects such as hemolysis when injected intravenously, thereby precluding any therapeutic benefits.
What is needed in the art is a drug-delivery system that can provide delivery of non-specific cytolytic peptides such as melittin to targeted tissues while preventing off-target effects. Such a system could be of great benefit in targeted drug-delivery, such as cancer therapy.